Positive effect on HRQoL and symptom severity with liso-cel in patients with R/R LBCL

Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy for the treatment of adults with relapsed or refractory large B-cell lymphoma (R/R LBCL) after ≥2 lines of therapy, was recently approved by the U.S. Food and Drug Administration (FDA). This approval was based on the phase I seamless TRANCEND-NHL-001 study, previously reported on the Lymphoma Hub.

Patient reported outcomes (PROs) are considered important for evaluating patients’ health-related quality of life (HRQoL). The Lymphoma Hub has published a discussion on the different instruments used to measure PROs, and findings from an earlier PRO assessment from the TRANSCEND-NHL-001 study are also available here. A further analysis assessing the HRQoL impact of liso-cel in patients with R/R LBCL based on TRANSCEND-NHL-001 was recently published by Patrick et al,¹ and the key findings are summarized below.   

Study design¹

PRO assessments were based on the ongoing open label, non-randomized, multicenter, multicohort seamless phase I TRANSCEND-NHL-001 study (NCT02631044) of liso-cel in patients with R/R LBCL. Assessments were conducted before treatment, at baseline, at 1, 2, 3, 6, 9, 12, 18, and 24 months, at disease progression, and at end of study. Analyses were conducted in PRO-evaluable sub-population of the liso-cel–treated LBCL patients using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30; n = 181) and EuroQol 5-Dimension 5-Level (EQ-5D-5L; n = 186) scores to assess HRQoL and health utility in patients. Clinically meaningful improvements were defined as a ≥10-point change from baseline in mean scores.

Results¹

Baseline characteristics

The median on-study follow-up period was 11.4 months (range, 1.2–27.8) for the EORTC QLQ-C30 evaluable patients. The mean time from diagnosis to first liso-cel infusion was 32.3 months (standard deviation [SD], 35.7). Most of the patients were white males who were non-Hispanic or Latino (as shown in Table 1).

Table 1. Baseline characteristics*

CR, complete response; DLBCL NOS, diffuse large B-cell lymphoma not otherwise specified; ECOG PS, Eastern Cooperative Oncology Group performance status; EORTC QLQ, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EQ-5D-5L, EuroQol 5-Dimension 5-Level; FL, follicular lymphoma; HGBCL, high-grade B-cell lymphoma; NHL, non-Hodgkin lymphoma; PMBCL, primary mediastinal B-cell lymphoma; PR, partial response; SD, standard deviation. *Adapted from Patrick et al.1
Characteristic	EORTC QLQ-C30 (n = 181)	EQ-5D-5L (n = 186)
Age, years               Mean (SD)               Median	60.2 (14.0) 63	60.1 (13.9) 63
Age group, %               <65 years               ≥65 years               <75 years               ≥75 years	58 42 90 10	59 41 89 11
Male/female, %	65/35	65/35
Race, %               White               Other               Unknown/missing	86 9 5	85 10 5
Ethnicity, %               Not Hispanic/Latino               Hispanic or Latino               Unknown	85 11 4	84 11 4
ECOG PS at screening, %               0               1               2	40 59 1	39 60 1
Pre–liso-cel ECOG PS, %               0               1               2               3	24 70 4 1	24 71 4 1
Type of B-cell NHL, %               DLBCL NOS               HGBCL               DLBCL transformed from iNHL               PMBCL               FL Grade 3b	54 10 28 7 1	53 11 27 8 1
Disease status, %               Refractory               Relapsed               Chemotherapy refractory               Chemotherapy sensitive	78 22 67 33	78 22 67 33
Best response to any prior therapy, %               CR               PR	59 29	59 28

EORTC QLQ-C30

Adherence to EORTC QLQ-C30 was 88%, 66%, 73%, and 69% at 1, 6, 12, and 18 months, respectively.

• A significant deterioration in physical functioning was observed in the first month after treatment (mean (SD) change of –4.8 (20.6) from baseline) but significant improvements were then seen at 2, 9, and 12 months, although these were not clinically meaningful.
• Clinically meaningful improvements were seen in global health status/QoL, fatigue, emotional functioning, and social functioning (as shown in Table 2).
  • Individual-level patient analysis revealed that clinically meaningful improvements were seen in global health status/QoL in 33% of patients at 1 month, 52% at 6 months, and 60% at both 12 and 18 months. The median time to first clinically meaningful improvement in global health status/QoL was 2.2 months (95% CI, 2.0–2.9).
  • Clinically meaningful improvements in fatigue scores were seen in 41%, 53%, 58%, and 60% patients at 1, 6, 12, and 18 months, respectively.
• Comparison of treatment responders (n = 137) vs non-responders (n = 44) showed a clinically meaningful improvement at any timepoint in global health status/QoL (72% vs 41%), physical functioning (42% vs 23%), fatigue (74% vs 45%), and pain (56% vs 41%).
• The median time to first clinically meaningful improvement was shorter in treatment responders compared to non-responders, for global health status/QoL (2 months [95% CI, 1.9–2.2] vs 3 months [95% CI, 2.3–not reached]) and for fatigue (1.9 months [95% CI, 1.7–2.1] vs 6.0 months [95% CI, 1.1–not reached]). 

Table 2. EORTC QLQ-C30 scores*

EORTC QLQ, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; SD, standard deviation. *Adapted from Patrick et al.1 †Positive change denotes improvement. ‡Negative change denotes improvement. §n = 147 (fatigue, pain, role, and physical functioning). Bold font indicates clinically meaningful improvement.
	Baseline n = 181	2 months n = 146§	6 months n = 93	9 months n = 84	12 months n = 62	18 months n = 25
	Mean (SD)
Global health status/QoL†	62.3 (20.3)	+11.9 (22.6)	+13.0 (21.7)	+13.3 (21.8)	+16.7 (21.2)	+19.7 (25.6)
Physical functioning†	77.8 (19.2)	+2.8 (18.0)	+2.9 (19.4)	+4.6 (20.8)	+7.0 (19.8)	+6.9 (22.7)
Fatigue‡	38.2 (21.8)	-10.2 (24.3)	-7.9 (27.3)	-9.9 (25.3)	-14.7 (27.2)	-15.1 (29.9)
Pain‡	25.6 (25.8)	-8.1 (26.1)	-3.1 (23.6)	-0.6 (28.4)	-7.0 (25.9)	-8.7 (29.7)
Role functioning†	67.3 (28.8)	+9.8 (30.1)	+5.7 (29.7)	+8.9 (30.2)	+10.5 (30.2)	+14.7 (33.1)
Emotional functioning†	83.0 (17.4)	+3.4 (16.5)	+3.5 (16.3)	+3.6 (17.1)	+6.4 (16.4)	+11.6 (18.1)
Cognitive functioning†	84.0 (17.8)	+6.7 (18.9)	+1.4 (18.5)	+2.2 (18.3)	+3.2 (21.3)	+9.3 (22.1)
Social functioning†	66.7 (27.7)	+10.1 (33.4)	+11.8 (31.6)	+14.3 (30.4)	+19.9 (33.0)	+20.7 (32.7)

EQ-5D-5L

An initial trend towards decrease in the mean EQ-5D-5L index score was seen at 1 month after liso-cel infusion; however, this significantly increased at 2, 12, and 18 months. The mean EQ-5D-5L visual analog scale score showed a trend of increasing from 2 through 18 months. The increases in mean EQ-5D-5L scores were not clinically meaningful.

Compared to non-responders, a higher proportion of treatment responders achieved a clinically meaningful improvement in EQ-5D-5L index scores at any point in time.

Conclusion

This study demonstrated that patients with R/R LBCL treated with liso-cel experienced short- and long-term improvements in HRQoL and symptom severity, extending to 12 months, across various EORTC QLQ-C30 scales. Moreover, clinically meaningful improvements were reported for a marked number of patients. However, the findings should be interpreted in the context of limitations that are inherent in assessing PROs in clinical trials.